CN113713871A

CN113713871A - Syringe

Info

Publication number: CN113713871A
Application number: CN202110987412.9A
Authority: CN
Inventors: 孙希财; 赵雄飞; 金宜强
Original assignee: Shanghai Angecon Biotechnology Co ltd
Current assignee: Shanghai Angecon Biotechnology Co ltd
Priority date: 2021-08-26
Filing date: 2021-08-26
Publication date: 2021-11-30

Abstract

The invention relates to the technical field of medical experimental instruments, and discloses an injector, which aims to solve the problems of complicated pretreatment steps, overlong time and the like of biological products, particularly cell products; the technical scheme provided by the invention is as follows: the syringe includes: the device comprises an upper section of a syringe barrel, a lower section of the syringe barrel, a push-pull pipe, a one-way valve part, a filtering membrane part, a small piston and a push-pull rod; the seven parts are concentric with the central axis. The one-way valve part and the filtering membrane part are positioned in the upper section part and are in sliding connection with the inner wall of the upper section part; when the small piston moves at the lower section part, the small piston is in sliding connection with the inner wall of the lower section part; the push-pull rod passes through the center of the one-way valve element and the center of the filter membrane element. The beneficial effects are that: the injector can be applied to various operations such as freezing storage, recovery, flushing, concentration, injection and the like of biological preparations, simplifies related processing steps, saves time, reduces pollution risks, and particularly improves concentration and flushing efficiency.

Description

Syringe

Technical Field

The invention relates to the technical field of medical experimental instruments, in particular to an injector; the present invention is particularly suitable for various operations on cell reagents.

Background

During the production, transportation and use processes of the biological product, the biological product needs to be concentrated, diluted, frozen and preserved and injected; the method improves the use efficiency of each operation link and reduces the infection risk of the use, and is a hot field of the current industry research; especially cell biological products, have more strict and high requirements on operation conditions.

Biological preparations, particularly cell preparations, are subjected to pretreatment steps such as cell cryopreservation, recovery, concentration and the like after manufacture and before formal application to patients. The pretreatment steps before the application of the biological product preparations are relatively separated, complicated and complex to operate, and have high requirements on the cleanliness of the operating environment and the aseptic operation of operators. If according to the traditional mode, not only is time and cost consumed, but also the preparation is easy to be polluted in the process, and the use is influenced.

Therefore, how to simplify various pretreatment steps of the preparation, shorten the preparation treatment time and reduce the possibility of pollution of the preparation is a key technical problem to be solved in the technical field at present.

Disclosure of Invention

The invention provides an injector, and aims to solve the problems of complicated pretreatment steps of biological products, particularly cell products, overlong treatment time, easy pollution of preparations and low concentration efficiency in the background.

The present invention is achieved in such a way that,

a syringe comprising a syringe barrel and a piston assembly;

the syringe barrel comprises an upper section part and a lower section part; the upper section part is positioned at the upper part and has a large diameter; the lower section is positioned at the lower part and has a small diameter;

the piston assembly comprises a large piston part and a small piston part;

the large piston part comprises: a one-way valve part, a filter membrane part, and a push-pull tube; the one-way valve part and the filtering membrane part are positioned in the upper section and are in sliding connection with the inner wall of the upper section;

the push-pull pipe, the one-way valve part and the filtering membrane part are sequentially arranged from top to bottom, and the adjacent parts are fixedly connected; or the push-pull pipe, the filtering membrane part and the one-way valve part are sequentially arranged from top to bottom, and the adjacent parts are fixedly connected;

the small piston part comprises an upper push-pull rod and a lower small piston which are fixedly connected; when the small piston moves at the lower section part, the small piston is in sliding connection with the inner wall of the lower section part;

the filter comprises an upper section part, a lower section part, a one-way valve part, a filter membrane part, a push-pull pipe, a push-pull rod and a small piston, wherein the upper section part, the lower section part, the one-way valve part, the filter membrane part, the push-pull pipe, the push-pull rod and the small piston share a common central axis;

the push-pull rod penetrates through the center of the one-way valve part and is connected with the one-way valve part in a sliding manner;

the push-pull rod penetrates through the center of the filtering membrane part and is connected with the filtering membrane part in a sliding mode.

The one-way valve component and the filtering membrane component are fixed together and are matched with the upper section of the syringe barrel to act. When the push-pull pipe is pulled upwards, the one-way valve component is equivalent to a large piston, and external liquid can be sucked through the lower section part. Under the condition that the lower section part is sleeved with the sealing protective sleeve and the preparation liquid is in the lower section part, when the push-pull pipe is pressed downwards, the liquid flowing through the filtering membrane part is filtered; the substances with the pore diameter larger than the filter pores of the filter membrane are left under the filter membrane, so that the concentration of the preparation under the filter membrane is improved; the filtrate overflows from the one-way valve part to the upper part of the one-way valve part and can be poured out.

The invention has the beneficial effects that:

1) the injector has the advantages of novel structure, simple and convenient operation, low cost, multiple functions of injection, filtration, concentration and freezing storage, and wide application.

2) The freezing, recovery, flushing, concentration and injection of the biological preparation are facilitated, and particularly, the operations of freezing, recovery, concentration, injection and the like of cells can be completed in the same injector; therefore, the pretreatment step before application is simplified, the operation time is saved, the pollution risk of the preparation is reduced, and the use efficiency is improved.

3) The biological preparation, especially cell preparation, can be concentrated, and the concentration treatment effect of the preparation is improved.

4) The biological preparation, especially the cell preparation, can be repeatedly washed, and the washing treatment efficiency of the preparation is improved.

Drawings

Figure 1 is one of the schematic views of the inventive syringe.

Fig. 2 is a sectional view of fig. 1.

Fig. 3 is a second schematic view of the syringe of the present invention.

Fig. 4 is an enlarged view of a portion of fig. 2 at I, on a 3:1 scale.

Fig. 5 is a third schematic view of the injector of the present invention.

Figure 6 is the fourth schematic view of the inventive syringe.

Figure 7 is a fifth schematic view of the inventive syringe.

Figure 8 is a sixth schematic view of the inventive syringe.

Fig. 9 is a schematic view of the components of the inverted funnel-shaped check valve.

Fig. 10 is a cross-sectional view of fig. 9.

Fig. 11 is a top view of fig. 9.

Fig. 12 is a bottom view of fig. 9.

Fig. 13 is one of the force diagrams of the inverted funnel shaped check valve component.

Fig. 14 is a second force diagram of the inverted funnel-shaped check valve component.

FIG. 15 is a seventh schematic view of the injector of the present invention, wherein the diameter of the connecting portion transitions from a larger diameter at the upper portion to a smaller diameter at the lower portion.

FIG. 16 is a schematic view of a membrane holder provided with two scallops.

FIG. 17 is a schematic view of a membrane holder provided with three scallops.

FIG. 18 is a schematic view of a membrane holder provided with six scallops.

Fig. 19 is a perspective view of fig. 18.

Figure 20 is a schematic view of the syringe of the invention with a stop lever.

Fig. 21 is a schematic view of the syringe of the present invention having an upper end portion with a circular arc shape.

FIG. 22 is a schematic view of the injector of the present invention having a frustoconical undercut in the lower section to facilitate entry of the small plunger into the lower section, as compared to FIG. 2.

Figure 23 is a schematic view of an inventive syringe sheathed with a protective sheath.

Fig. 24 is a schematic view of the syringe of the invention with the needle attached.

FIG. 25 is a schematic view of a large and small piston using a steel ball type check valve, in which the push-pull tube and the upper portion of the syringe barrel are omitted and not shown.

FIG. 26 is a schematic view of the steel ball-type check valve of FIG. 25.

Fig. 27 is a cross-sectional view of fig. 26.

Fig. 28 is a cross-sectional view of the cover of fig. 26.

Fig. 29 is a top view of fig. 28.

Fig. 30 is a cross-sectional view of the base of fig. 26.

Fig. 31 is a top view of fig. 30.

Fig. 32 is a bottom view of fig. 30.

Figure 33 is a schematic view of a base with two one-way valve structures open.

Figure 34 is a schematic view of a base with three check valve structures.

Description of the figures

100. A syringe barrel; 101. an upper section; 102. a lower section; 103. a limiting handle; 104. calibration; 105. a protective sleeve; 107. a connecting portion; 201. pushing and pulling the pipe; 202. a reverse funnel shaped check valve component; 203. a large piston handle; 301. a push-pull rod; 302. a small piston; 303. a small piston handle; 401. filtering the membrane; 402. a membrane scaffold; 403. a sector hole; 204. a steel ball type check valve; 206. stainless steel balls; 204b. a base; 204a, a cover body; 204b-1. a through hole; 204a-1. a shielding hole; 204a-2, drain hole.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

The invention relates to a general technical scheme. A syringe comprising a syringe barrel 100 and a plunger assembly;

the syringe barrel 100 comprises an upper section 101 and a lower section 102; the upper section 101 is positioned at the upper part and has a large diameter; the lower section 102 is positioned at the lower part and has a small diameter;

the piston assembly comprises a large piston part and a small piston part;

the large piston part comprises: a check valve part, a filter membrane part, and a push-pull tube 201; the one-way valve part and the filtering membrane part are positioned in the upper section part 101 and are in sliding connection with the inner wall of the upper section part 101;

the push-pull pipe 201, the one-way valve part and the filtering membrane part are arranged from top to bottom in sequence, and the adjacent parts are fixedly connected; or the push-pull pipe 201, the filtering membrane part and the one-way valve part are arranged from top to bottom in sequence, and the adjacent parts are fixedly connected;

the small piston part comprises an upper push-pull rod 301 and a lower small piston 302 which are fixedly connected; when the small piston 302 moves in the lower section 102, the small piston 302 is connected with the inner wall of the lower section 102 in a sliding way;

the filter comprises an upper section part 101, a lower section part 102, a one-way valve part, a filter membrane part, a push-pull pipe 201, a push-pull rod 301 and a small piston 302, wherein the seven parts have a common central axis;

the push-pull rod 301 penetrates through the center of the one-way valve part, and the two are connected in a sliding manner;

the push-pull rod 301 passes through the center of the filter membrane element and is connected with the filter membrane element in a sliding manner.

The above general solution is now explained as follows.

First, the shape and structure and mechanical operation of the syringe of the present invention will be explained.

Figure 1 is one of the schematic views of the inventive syringe. Fig. 2 is a sectional view of fig. 1. In contrast to fig. 2, the second schematic view of the injector of fig. 3 shows the small piston 302 moving downward under the downward pushing action of the push-pull rod 301. Fig. 4 is an enlarged view of a portion of fig. 2 at I, on a 3:1 scale. Fig. 5 is a third schematic view of the syringe of the present invention, in which the large piston portion (check valve part, filtering membrane part, push-pull tube 201) and the small piston portion (push-pull rod 301, small piston 302) are moved downward in comparison with fig. 2. Fig. 6 is a fourth schematic view of the injector of the present invention, in contrast to fig. 5, in which the small piston 302 is moved downward by the downward pushing of the push-pull rod 301. Fig. 7 is a fifth schematic view of the syringe of the present invention, in which the large piston portion (check valve part, filtering membrane part, push-pull tube 201) and the small piston portion (push-pull rod 301, small piston 302) are moved upward in comparison with fig. 2. Fig. 8 is a sixth schematic view of the injector of the present invention, in contrast to fig. 7, in which the small piston 302 is moved downward by pushing the push-pull rod 301 downward.

FIG. 9 is a schematic view of an inverted funnel-shaped check valve component 202 made of a resilient, low temperature resistant material; FIG. 10 is a cross-sectional view of FIG. 9; FIG. 11 is a top view of FIG. 9; fig. 12 is a bottom view of fig. 9.

In the present invention, the filter membrane 401 is also called a filter membrane.

Second, the operation of the preparation with the syringe of the invention will be described in five categories, 1, 2, 3, 4 and 5.

1. The operation of sucking up the preparation by the syringe can be performed in the following steps a, b and c.

a. The syringe is in the condition of figure 5.

b. The lower port of the lower syringe section 102 is extended into the preparation liquid.

c. The large piston portion (check valve element, filter membrane element, push-pull tube 201) and the small piston portion (push-pull rod 301, small piston 302) are pulled up together to the position shown in fig. 7, and thus the preparation liquid is sucked into syringe barrel 100.

And (4) explanation. Because the check valve part and the filtering membrane part are fixedly connected together, the check valve part and the filtering membrane part are in sliding connection with the inner wall of the upper section part 101; when they are pulled upward, a large piston is drawn upward, which has the effect of drawing a vacuum in syringe barrel 100, so that the formulation liquid can be drawn into syringe barrel 100.

Also, at rest, the push-pull rod 301 is surrounded by the one-way valve element to be airtight; the air-tight effect is better when pulled upwards, as further explained in connection with fig. 13. Fig. 13 is a diagram showing the check valve element 202 in the shape of an inverted funnel when pulled upward, and this corresponds to the effect of vacuum pumping, and the inner diameter of the upper port of the check valve element tends to become smaller, so that the push-pull rod 301 is more tightly surrounded by the check valve element 202, and the air-tight effect is better.

2. After the preparation liquid is sucked into the syringe, the preparation can be concentrated according to the following steps d and e.

d. The sheath 105 is put on to prevent the liquid of the preparation from flowing out. The so-called jacketing may be achieved by a relatively tight dimensional fit between the inner diameter of the protective jacket 105 and the outer diameter of the lower section 102; or the two can be provided with threads, and the connection can be realized by a threaded connection, namely the connection is formed by screwing in the threads.

e. The large piston part (check valve part, filter membrane part, push-pull tube 201) and the small piston part (push-pull rod 301, small piston 302) are pushed together downward from fig. 7 to the position of fig. 2. As it is pushed downward, the formulation liquid under filter membrane 401 is concentrated.

And (4) explanation. When the large piston is pushed down, the liquid passes through the filter membrane 401, and substances having a diameter larger than that of the filter pores are retained, thereby concentrating the preparation under the filter membrane 401. Also, when the large piston portion is pushed down, the check valve element 202 receives upward pressure from the liquid, which causes the upper port of the check valve element to become large, as shown in fig. 14, causing a gap to occur between the upper port and the push-pull rod 301, and the filtered liquid flows upward through the gap.

Through the operation, the concentration of the preparation on the lower side of the filter membrane 401 is improved; if the target concentration has not been reached, the sleeve 105 can be removed, the raw material preparation can be aspirated again and then concentrated. This can be done one or more times until the target concentration is reached, during which time the liquid on the upper side of the large piston part can overflow and be poured into a container for collecting waste liquid.

3. After the preparation liquid is concentrated by using the syringe, the preparation liquid can be frozen and stored in a specified mode and then recovered. It should be noted that, with the syringe of the present invention, the same syringe can be continuously used for cryopreservation and subsequent resuscitation after the preparation is concentrated without replacing the device, thereby reducing the procedures and devices, reducing the risk of contamination of the preparation, and improving the working efficiency.

Typically, the formulation is concentrated and then frozen after being sheathed in a protective sheath 105. When necessary, the cells are thawed and revived in a specified manner and then used again.

4. The concentrated preparation can be injected into other preparation to be prepared by removing the protective sleeve 105, or loading a needle and injecting into a recipient.

5. Washing: some cells need to be washed, and by using the injector of the present invention, the small piston 302 is firstly pulled to the uppermost end of the lower section 102, and then the large piston and the small piston are pulled together, so as to suck a certain amount of cell sap; immediately thereafter, a certain amount of the washing liquid is sucked again, then the small piston 302 is slid to the port of the lower section 102 to block the port, then the large piston section is pressed, the washing liquid overflows from the check valve member, the overflowing washing liquid remains at the upper end of the large piston section, and then the above operations are continuously repeated, thereby completing the repeated washing of the cells.

The "sliding the small piston 302 to the port of the lower section 102 to block the port" operation is to prevent the liquid from flowing out of the lower section 102. The same function can be achieved if the action of the "sliding small piston 302" is replaced by the sheathing of the protective sheath 105.

6. Also, when all the parts are in a static state, the liquid is blocked at the check valve part, i.e. the liquid cannot flow through the check valve part.

The general technical solution of the present invention has been described and illustrated above. In the following, further technical solutions are described and illustrated.

Further technical scheme 1.

Technical solution description. The syringe comprises other parts, and the other parts are in any one of the following three conditions: a. a protective sheath 105; b. a needle assembly; c. a protective sheath 105 and a needle assembly.

And (5) explaining a technical scheme. The needle assembly may be made of a transparent, freeze-resistant plastic for the needle base and needle cover, while the needle is made of stainless steel. The protective sleeve 105 or needle assembly can facilitate use of the syringe, the needle assembly facilitates liquid suction and injection of the syringe, and the protective sleeve 105 facilitates storage of liquid carried by the syringe, repeated flushing and concentration of the preparation and other processes. The syringe may be covered with only the needle, or only the protective cover 105 to seal the lower section 102, or the needle may be covered first and then the protective cover 105 is covered on the needle, or the protective cover 105 covers the needle and the lower section 102 together.

Further technical scheme 2.

Technical solution description. The syringe barrel 100 is provided with a scale 104, and the specific setting condition is any one of the following three conditions: a. the scale 104 is arranged on the upper section 101; b. the scale 104 is arranged on the lower section 102; c. the scale 104 is provided in the upper stage part 101 and the lower stage part 102.

And (5) explaining a technical scheme. The scale 104 is arranged, so that the inhalation, injection and rapid operation according to the volume can be convenient.

Further technical scheme 3.

Technical solution description. The syringe barrel 100 is transparent.

And (5) explaining a technical scheme. The syringe barrel 100 is transparent, so that the operation state of the syringe can be observed conveniently.

Further technical scheme 4.

Technical solution description. The syringe barrel 100 includes a connecting portion 107 connecting the upper section 101 and the lower section 102, wherein the diameter of the connecting portion 107 is changed from the diameter of the upper section 101 to the diameter of the lower section 102.

And (5) explaining a technical scheme. The description will be made with reference to fig. 15. The connection 107 has a diameter that transitions from the upper section 101 to the lower section 102, which may further facilitate the sliding of the small piston 302 into the lower section 102.

Further technical means 5.

Technical solution description. The check valve part is in an inverted funnel shape, and the port at the upper part of the check valve part is elastic and is in sliding connection with the push-pull rod 301; the push-pull rod 301 passes through the port in the upper portion of the check valve part and is slidably connected thereto.

The technical scheme is explained as follows.

First, the push-pull tube 201 and the inverted funnel-shaped check valve element 202 are in a rest state. The stationary state means that the two members do not move up and down relative to the upper stage part 101. The inverted funnel-shaped check valve element 202 has elasticity at its upper end, so that the push-pull rod 301 is sealingly surrounded by the end; on the other hand, the push-pull rod 301 can slide up and down in the port by pushing and pulling the push-pull rod by an external force.

Secondly, after the liquid is inserted into the lower port of the lower section 102, if the push-pull tube 201 drives the inverted funnel-shaped check valve component 202 to move upward, the situation is as follows: a. the upper end of the inverted funnel-shaped one-way valve element 202, which still sealingly embraces the push-pull rod 301. b. The check valve element 202 acts as a large piston to draw in fluid.

FIG. 13 is a force diagram of the inverted funnel shaped check valve member 202 as it is pulled upwardly, with the force directed downwardly; therefore, the inner diameter of the upper port of the inverted funnel-shaped check valve element 202 tends to become smaller, so that the push-pull rod 301 is held more tightly by the check valve element 202, and the sealing effect is better.

Thirdly, when the liquid is sucked by the syringe and the lower section 102 is sleeved with the sealed protective sleeve 105, if the push-pull tube 201 drives the one-way valve element 202 with the inverted funnel shape to move downwards, the situation is as follows: the inverted funnel-shaped check valve component 202 is subjected to the upward pressure of the liquid (including air) below, causing the inner diameter of the upper port of the check valve component 202 to expand and form a gap, and the liquid (including air) passes through the filter membrane component, through the gap, and over the inverted funnel-shaped check valve component 202.

FIG. 14 is a force diagram of the inverted funnel shaped check valve part 202 as it moves downward; this pressure comes from the liquid below (including air). Under the pressure of the liquid (including air), the upper port of the inverted funnel-shaped check valve element 202 becomes large, causing a gap to occur between the upper port and the push-pull rod 301, from which the filtered liquid (including air) flows upward.

Further technical scheme 6.

Technical solution description. The filtering membrane parts comprise a filtering membrane 401 and a membrane bracket 402.

And (5) explaining a technical scheme. Filter membrane 401 is also known as a filter membrane. Filter membrane 401 belongs to flexible part itself, and filter membrane 401 depends on and is fixed in membrane support 402, can normally work. The fixed connection of the filter membrane 401 and the membrane bracket 402 can be realized by a snap ring of the outer package or by an adhesive.

The membrane holder 402 may be a single layer or may be an upper layer or a lower layer.

Different filtration membranes 401 can be used to achieve different filtration objectives. For example, filter 401 may filter different agents; the cell filter is selected and the cell preparation can be filtered.

Further technical scheme 7.

Technical solution description. The membrane holder 402 comprises an upper layer and a lower layer, and the filter membrane 401 is sandwiched between the upper layer and the lower layer.

And (5) explaining a technical scheme. As described in conjunction with FIG. 4, the membrane holder 402 is divided into an upper layer and a lower layer, and the filter membrane 401 is sandwiched between the upper layer and the lower layer, so that the structure of the filter membrane 401 is more stable.

The membrane holder 402 and the filter membrane 401 may be fixedly connected by an adhesive. A snap-fit arrangement may also be provided between the upper and lower layers of the membrane holder 402, thereby achieving a secure connection.

Further technical scheme 8.

Technical solution description. The diameter of the filter pores of the filter membrane 401 is 0.22 μm.

And (5) explaining a technical scheme. The filter 401 has a pore diameter of 0.22 μm, and if used for filtering cell preparations, is convenient for filtering various cells with a cell diameter larger than 0.22 μm, such as human neural stem cells with a diameter of 10-20 μm.

Further technical solution 9.

Technical solution description. The membrane bracket 402 is provided with more than two fan-shaped holes 403; the fan-shaped holes 403 are distributed rotationally symmetrically around the central axis of the membrane holder 402.

And (5) explaining a technical scheme. The fan-shaped holes 403 are rotationally and symmetrically distributed around the central axis of the membrane support 402, the structure facilitates the design and manufacture of the membrane support, improves the stability of liquid flow in the use process, and ensures that the liquid is more smooth and balanced in the flow process.

FIG. 16 is a schematic view of a membrane holder 402 provided with two scallops 403; FIG. 17 is a schematic view of a membrane holder 402 provided with three scallops 403; FIG. 18 is a schematic view of a membrane holder 402 provided with six scallops 403;

fig. 19 is a perspective view of fig. 18.

Further technical means 10.

Technical solution description. The injector is made of low-temperature resistant materials.

And (5) explaining a technical scheme. Use of the inventive syringe, if a low temperature environment is involved, e.g., the syringe needs to be cryopreserved along with the formulation in the container, etc., the syringe needs to be made of a low temperature resistant material.

The following describes materials used for the components:

the syringe barrel 100, the push-pull tube 201 and the push-pull rod 301 can be made of transparent freeze-resistant plastics; the check valve part (including the inverted funnel-shaped check valve part 202), the membrane holder 402 may be made of low temperature resistant silicone rubber; the filter 401 and the cell filter may be made of polytetrafluoroethylene; the protective sheath 105 may be made of transparent, freeze-resistant plastic or low temperature resistant silicone rubber.

In the needle assembly, the needle base and needle cover may be made of transparent, freeze-resistant plastic, and the needle may be made of stainless steel.

The low temperature resistant plastic (freezing resistant plastic) can be POM type low temperature resistant plastic produced by Shanghai Minghuang plastics science and technology limited.

The low-temperature resistant silicone rubber (freezing-resistant silicone rubber) can be low-temperature resistant silicone rubber produced by Dongguan city and Yingnig plastic raw material limited company.

Further technical solution 11.

Technical solution description. The injector is used for any combination of four operations; the four operations are as follows: injection of the cell preparation, washing of the cell preparation, cryopreservation of the cell preparation, and concentration of the cell preparation.

And (5) explaining a technical scheme.

There are 4 types of arbitrary combinations of the four operations, and 15 types of the arbitrary combinations are listed below.

The 1 st category is a single job, and there are 4 cases: a; b; c; d;

the 2 nd main category is two combined operations, and there are 6 cases: a + b; a + c; a + d; b + c; b + d; c + d;

the 3 rd main category is three combined jobs, and there are 4 cases: a + b + c; a + b + d; a + c + d; b + c + d;

the 4 th main category is four-combination work, and there are 1 cases: a + b + c + d.

In the above case, the operation a is an injection operation of the cell preparation; b, washing the cell preparation; the operation c is a freezing storage operation of the cell preparation, which comprises a recovery operation; the operation d is a concentration operation of the cell preparation.

The following describes the above 15 cases.

1 st operation a: and (4) injecting a cell preparation. The cell preparation can be injected into a recipient or a preparation to be prepared, etc. by pressing the large piston portion and the small piston 302.

The 2 nd operation b: and (5) washing the cell preparation. Some cells need to be washed, as will be described below. With the syringe of the present invention, the small piston 302 is moved into the lower section 102, and then the large and small pistons are pulled together to suck the cellular fluid to be flushed, and then the flushing fluid is sucked. Then sliding the small piston 302 into the lower section 102 of the syringe barrel 100, thereby plugging the lower section 102; then, the large piston portion is pressed downward, the cleaning liquid overflows from the upper portion of the check valve member, and the overflowing cleaning liquid is poured off, so that the first flushing is completed. If the first washing does not reach the target degree, the cleaning liquid can be sucked again for washing, or the cleaning liquid can be sucked again for washing until the target degree is reached.

In fig. 2, the space between the upper end of the upper stage 101 and the push-pull pipe 201 is not closed, and the used waste cleaning solution can flow out. In fig. 20, the space between the stopper handle 103 and the push-pull tube 201 is similarly not closed, and the used waste cleaning solution can be discharged.

Operation No. 3 c: frozen storage of cell preparations. Before freezing, the cell preparation needs to be added into a cell freezing medium to become a cell liquid, and then the cell liquid is frozen and stored.

The injector is used for freezing and storing the cell liquid in the injector; the cell liquid contains a cell preparation and a cell-containing cryopreservation solution. Further, the recovery process after the freezing storage is also carried out by keeping the cell liquid in the injector of the invention. Note: the recovered cell liquid can be continuously concentrated in the same syringe, so that the cell preparation is obtained.

Operation No. 4: concentration of the cell preparation.

The four operation conditions of a, b, c and d are described above. The following describes eleven other operating conditions.

The 5 th to 10 th cases are 6 cases of the work performed on the two combinations a, b, c, d, such as the work performed on the two combinations a + b, and so on. The operation of combining a and b means that the operation a (injection of the cell preparation) and the operation b (washing of the cell preparation) are performed using the syringe of the present invention, but there is no limitation in the order of the operation a and the operation b, and the operation a and the operation b may be performed first and the operation b may be performed later, as the case requires.

The 11 th to 14 th types are operations performed on the combinations a, b, c, and d.

The 15 th type is a job performed by four combinations, i.e., a + b + c + d four combinations.

Now, the description will be given by way of example. The three combinations will be described by taking 100. mu.l of human neural stem cells at an appropriate concentration as an example. 100 microliters of human neural stem cell fluid is firstly sucked by the syringe, then 900 microliters of cell cryopreservation fluid is sucked, the protective sleeve 105 is sleeved on the syringe, and the syringe is used for performing liquid nitrogen cryopreservation. After recovery, the large piston part is pressed to overflow 900 microliters of solution to the upper part of the one-way valve part through the one-way valve part, and 100 microliters of concentrated human neural stem cell fluid remains in the syringe barrel 100. Then, the protective sheath 105 was removed, and 100. mu.l of the human neural stem cell liquid in the canister was injected into the human body.

Further description and introduction. The internal volume of the lower section 102 can be designed to accommodate just 100 microliters of space, which is more convenient to operate, and when the large piston section descends to the lowest end of the upper section 101, the concentrated cell liquid remaining in the lower section 102 is about 100 microliters, and the injection is completed by pushing the small piston 302. The foregoing examples relate to the freezing storage (operation c) of a cell preparation, the concentration (operation d) of a cell preparation, and the injection (operation a) of a cell preparation; therefore, in the above example, the operator performed the operation of the combination a + c + d using the syringe of the present invention.

Further technical means 12.

Technical solution description. The upper end of the upper section part 101 is provided with a limiting handle 103.

And (5) explaining a technical scheme. FIG. 20 is a schematic view of the inventive syringe provided with a stopper handle 103; the limiting handle 103 is in threaded connection with the upper section 101 of the syringe barrel 100.

Assembling: 1. sleeving the limiting handle 103 on the upper part of the push-pull pipe 201 for later use; 2. assembling a push-pull pipe 201, an inverted funnel-shaped one-way valve part 202, a membrane bracket 402 and a filter membrane 401; 3. assembling the push-pull rod 301 and the small piston 302; 4. placing the assembled components into the upper section 101; 5. the screw thread of the limit handle 103 is screwed into the screw thread of the upper section 101. And finishing the assembly.

The advantage of providing a stop handle 103 is that it prevents the push-pull tube 201 or the like from being pulled out of the syringe barrel 100.

Further technical solution 13.

Technical solution description. The upper end of the push-pull pipe 201 is provided with a large piston handle 203.

And (5) explaining a technical scheme. The large piston handle 203 is not needed, the operation can be performed, but the operation is inconvenient. The large piston handle 203 is provided, and the operation is convenient.

Further technical means 14.

Technical solution description. The upper end of the push-pull rod 301 is provided with a small piston handle 303.

And (5) explaining a technical scheme.

The operation can be performed without the small piston handle 303, but the operation is inconvenient. The small piston handle 303 is arranged, so that the operation is convenient.

Further technical solution 15.

Technical solution description. The head of the small piston 302 is conical or arc-shaped.

And (5) explaining a technical scheme. The head of the small plunger 302 is tapered or curved to facilitate the small plunger 302 entering the lower section 102 of the syringe barrel 100.

Further technical means 16.

FIG. 21 is a schematic view of the injector of the present invention with the bottom end of the upper section 101 being rounded; the lower end of the upper stage 101 in this figure is different from that in fig. 2.

Fig. 22 is a schematic view of the injector of the present invention having a frustoconical undercut in the lower section 102, which facilitates entry of the small plunger 302 into the lower section 102, as compared to fig. 2.

Figure 23 is a schematic view of the inventive syringe sheathed with a protective sheath 105.

Example one

In this example, a polytetrafluoroethylene membrane manufactured by Guangzhou Jiete biofiltration GmbH was used as the cell filtration membrane. The polytetrafluoroethylene material has good heat resistance and cold resistance, can be used at minus 180-260 ℃ for a long time, and further enables the cell filter membrane to still maintain good filtering performance after low-temperature liquid nitrogen freezing and recovery; after filtration through a cell membrane, the cell sap is concentrated.

The diameter of the human neural stem cells ranges from 10 to 20 mu m, and when the cell liquid of the human neural stem cells is concentrated, a cell filter membrane with the diameter of a filter hole of 0.22 mu m can be selected to concentrate the cell liquid. FIG. 18 is a schematic view of a membrane holder 402 provided with six scallops 403; the plurality of fan-shaped holes 403 can facilitate the liquid to pass through, and the filtering efficiency is improved. The cell filter membrane is arranged between the two membrane brackets 402, which can prevent the cell filter membrane from generating large deformation when filtering and influencing the filtering effect of the cell filter membrane.

Syringe barrel 100 is made of a transparent, freeze-resistant plastic to facilitate viewing of cellular fluids inside syringe barrel 100. The scale 104 facilitates viewing the volume of cellular fluid. The protective sleeve 105, the small piston 302, the membrane bracket 402 and the inverted funnel-shaped check valve part 202 are all made of low-temperature resistant silicon rubber; the low-temperature resistant silicone rubber can be low-temperature resistant silicone rubber produced by Dongguan city and Yingnig plastic raw material Co.

The push-pull pipe 201 and the push-pull rod 301 are both made of low-temperature resistant plastics; the low temperature resistant plastic can be POM type low temperature resistant plastic produced by Shanghai Minghuang plastics science and technology limited.

Relevant parts in the embodiment are made of corresponding low-temperature-resistant materials, so that the injector disclosed by the invention is resistant to low temperature integrally. After the cell preparation and the cell freezing medium are sucked by the injector of the invention, the whole body is frozen into liquid nitrogen. When the liquid nitrogen is needed to be used, the liquid nitrogen is taken out from the liquid nitrogen and used after the relevant operation flow. For example, after thawing and thawing, the liquid in the syringe of the invention may be directly concentrated and filtered, and then the cell concentrate in the syringe may be directly injected. In contrast to the conventional techniques, after thawing the cells, they are further concentrated under sterile conditions with additional tools and then drawn into the prior art syringe for injection. Therefore, the syringe of the invention can reduce operation and change tools, not only improve efficiency, but also reduce the chance of infection.

Example two

This embodiment will be described in the case where the check valve component is a steel ball type check valve 204. Fig. 25 is a schematic view of a large and small piston using a steel ball type check valve 204, and in this figure, the push-pull tube 201 and the upper stage 101 of the syringe barrel 100 are not shown. Fig. 26 is a schematic view of the steel ball-type check valve 204 of fig. 25. Fig. 27 is a cross-sectional view of fig. 26. Fig. 28 is a cross-sectional view of the cover 204a of fig. 26. Fig. 29 is a top view of fig. 28. Fig. 30 is a cross-sectional view of the base 204b of fig. 26. Fig. 31 is a top view of fig. 30. Fig. 32 is a bottom view of fig. 30.

First, description and illustration of the shape structure of the steel ball type check valve 204.

As shown in fig. 25 to 32, the check valve component is a steel ball type check valve 204; the steel ball type check valve 204 includes: a stainless steel ball 206, a base 204b, and a cover 204 a; the steel ball type one-way valve 204 is provided with more than two one-way valve structures; the check valve structures are rotationally and symmetrically distributed around the central axis; each check valve structure is provided with a hollowed-out truncated cone-shaped structure on a base 204b, a stainless steel ball 206 is placed at the hollowed-out position, a through hole 204b-1 is formed in the hollowed-out position in a downward mode, and groove-shaped channels are formed in two sides of the upper portion of the hollowed-out position; in each one-way valve structure, a shielding hole 204a-1 and two drain holes 204a-2 are formed in a cover body 204 a; the shielding hole 204a-1 is positioned at the top of the stainless steel ball 206, and the diameter of the shielding hole is smaller than that of the stainless steel ball 206; drain hole 204a-2 is in communication with the fluted passage; the cover 204a and the base 204b are fixedly connected; the push-pull pipe 201, the steel ball type one-way valve 204 and the filtering membrane part are arranged from top to bottom in sequence, and adjacent parts are fixedly connected; the steel ball type one-way valve 204 is connected with the inner wall of the upper section part 101 in a sliding way; the push-pull rod 301 passes through the center of the steel ball type check valve 204, and the two are slidably connected.

The base 204b and the cover 204a can be fixedly connected by an adhesive; the stainless steel ball 206 needs to be placed before the attachment is secured.

In this embodiment, the steel ball check valve 204 is provided with four check valve structures, which are uniformly distributed on the circumference around the central axis, and the adjacent check valve structures have an angle of 90 ° on the circumference.

If surpassing the present embodiment, fig. 33 is a schematic view of a base 204b provided with two check valve structures, and fig. 34 is a schematic view of a base 204b provided with three check valve structures.

Secondly, the operation of the steel ball type check valve 204 is explained and introduced.

1. If the lower port of the lower section 102 of the syringe is inserted into the liquid preparation and the large piston part (the steel ball-type check valve 204, the filter membrane part, the push-pull tube 201 and the small piston part (the push-pull rod 301 and the small piston 302) are pulled upward, the liquid preparation is sucked into the syringe barrel 100.

Further explanation is provided. Because the steel ball type check valve 204 and the filtering membrane component are slidably connected with the inner wall of the upper section 101, when they are pulled upwards, a large piston is drawn upwards, and a vacuum pumping effect is provided in the syringe barrel 100, so that the preparation liquid can be sucked into the syringe barrel 100. In the process of upward drawing, the stainless steel balls 206 in each one-way valve structure are subjected to triple actions of rubber pressure, gravity and vacuum pulling force (the force is downward) around the shielding hole 204a-1 to block the through hole 204b-1 below the truncated cone-shaped hollow.

2. After the preparation liquid is sucked into the syringe, the following operation is performed in order to concentrate the preparation.

First, the sheath 105 is pulled over to prevent the formulation liquid from flowing out.

Then, the large piston part (steel ball type check valve 204, filter membrane part, push-pull tube 201 and small piston part (push-pull rod 301, small piston 302)) are pushed downward together, and thus the preparation liquid under the filter membrane 401 is concentrated.

Further explanation is provided. When the large piston portion is pushed down, the stainless steel ball 206 in each check valve structure is subjected to upward pressure from the liquid, and the upward pressure causes the stainless steel ball 206 to rise and push up the shielding hole 204a-1, so that the rubber around the shielding hole 204a-1 is obviously deformed in an upward protruding manner, but the deformation does not cause the stainless steel ball 206 to run out of the shielding hole 204a-1. After the stainless steel ball 206 is lifted, the liquid flows out of the steel ball type one-way valve 204 along the through hole 204b-1, the periphery of the stainless steel ball 206, the groove-shaped channel and the drain hole 204 a-2; thus, the concentration of the formulation below filter 401 is concentrated.

In addition, when the steel ball type check valve 204 is in a static state, the rubber around the shielding hole 204a-1 presses the stainless steel ball 206, so that the through hole 204b-1 below the stainless steel ball 206 is blocked.

And thirdly, materials used in the manufacturing of the steel ball type check valve 204 are explained.

The base 204b and the cover 204a are made of low temperature resistant silicone rubber, and then the two are fixedly connected through an adhesive or a snap structure.

The low-temperature resistant silicone rubber can be low-temperature resistant silicone rubber produced by Dongguan city and Yingnig plastic raw material Co.

EXAMPLE III

This example illustrates and describes the practice of the present invention in terms of the procedures of freezing, thawing, concentrating, injecting, etc. of a cell preparation of human neural stem cells.

The cell diameter of the human neural stem cell is 10-20 μm, and a 0.22 μm cell filter membrane is used for this purpose.

The operation was performed as follows.

1. A cell sap (hereinafter referred to as a cell sap) of the human neural stem cells is prepared.

2. The needle is installed.

3. Pressing the large piston part to the bottommost end of the upper section part 101; the small piston 302 is pressed into the lower section 102 and bottoms out.

4. The push-pull rod 301 is pulled first to pull the small piston 302 to the uppermost position of the lower section 102, and the cellular fluid is sucked into the lower section 102. Then, the large piston part and the small piston part are simultaneously pulled, and cell frozen stock solution (hereinafter referred to as frozen stock solution) is sucked; thus, the lower side of the upper stage part 101 and the lower stage part 102 generate a mixed liquid; the mixed liquid means: a mixed liquid of the cell liquid and the frozen stock solution. The cell fluid intake amount, frozen stock solution intake amount, and mixed fluid production amount can be directly obtained by the scale 104 or can be obtained by calculation.

5. After the above inhalation is completed, the protective cover 105 is worn, and the syringe with the mixed liquid is put into liquid nitrogen for freezing.

6. When the injector is needed, the injector is taken out of the liquid nitrogen, and the cell is thawed according to the cell thawing flow and conditions. After thawing, the push-pull tube 201 is pressed to concentrate the liquid in the syringe; the aforementioned pressing can be performed by means of the scale 104.

The useless solution filtered by the cell filter membrane overflows through the upper opening of the inverted funnel-shaped one-way valve part 202; or the useless solution filtered by the cell filter membrane overflows upwards through the steel ball type one-way valve 204.

7. The protective sleeve 105 is opened, and the small piston 302 is pushed into the lower section, so that the injection of the cell concentrated solution is completed.

Claims

1. A syringe comprising a syringe barrel (100) and a plunger assembly, characterized in that:

the syringe barrel (100) comprises an upper section (101) and a lower section (102); the upper section (101) is positioned at the upper part and has a large diameter; the lower section (102) is positioned at the lower part and has a small diameter;

the piston assembly comprises a large piston part and a small piston part;

the large piston part comprises: a one-way valve part, a filter membrane part, and a push-pull tube (201); the one-way valve part and the filtering membrane part are positioned in the upper section (101) and are in sliding connection with the inner wall of the upper section (101);

the push-pull pipe (201), the one-way valve part and the filtering membrane part are arranged from top to bottom in sequence, and the adjacent parts are fixedly connected; or the push-pull pipe (201), the filtering membrane part and the one-way valve part are sequentially arranged from top to bottom, and the adjacent parts are fixedly connected;

the small piston part comprises an upper push-pull rod (301) and a lower small piston (302), and the upper push-pull rod and the lower small piston are fixedly connected; when the small piston (302) moves in the lower section part (102), the small piston (302) is connected with the inner wall of the lower section part (102) in a sliding way;

the filter comprises an upper section (101), a lower section (102), a one-way valve part, a filter membrane part, a push-pull pipe (201), a push-pull rod (301) and a small piston (302), wherein the seven parts have a common central axis;

the push-pull rod (301) penetrates through the center of the one-way valve part, and the two are connected in a sliding manner;

the push-pull rod (301) penetrates through the center of the filtering membrane part, and the two are connected in a sliding mode.

2. A syringe as claimed in claim 1, wherein: the syringe comprises other parts, and the other parts are in any one of the following three conditions:

a. a protective sheath (105);

b. a needle assembly;

c. a protective sheath (105) and a needle assembly.

3. A syringe as claimed in claim 1, wherein: the syringe barrel (100) is provided with a scale (104), and the specific setting condition is any one of the following three conditions:

a. the scale (104) is arranged on the upper section (101);

b. the scale (104) is arranged on the lower section (102);

c. the scale (104) is provided on the upper stage part (101) and the lower stage part (102).

4. A syringe as claimed in claim 1, wherein: the syringe barrel (100) is transparent.

5. A syringe as claimed in claim 1, wherein: the syringe barrel (100) comprises a connecting part (107) which is connected with the upper section part (101) and the lower section part (102), and the diameter of the connecting part (107) is transited from the diameter of the upper section part (101) to the diameter of the lower section part (102).

6. A syringe as claimed in claim 1, wherein: the check valve part is in an inverted funnel shape, and the port at the upper part of the check valve part is elastic and is in sliding connection with the push-pull rod (301);

the push-pull rod (301) passes through the port at the upper part of the one-way valve part and is connected with the one-way valve part in a sliding way.

7. A syringe as claimed in claim 1, wherein: the check valve part is a steel ball type check valve (204);

the steel ball type check valve (204) comprises: a stainless steel ball (206), a base (204b), and a cover (204 a);

the steel ball type one-way valve (204) is provided with more than two one-way valve structures; the check valve structures are rotationally and symmetrically distributed around the central axis;

each one-way valve structure is characterized in that a base (204b) is provided with a hollowed-out truncated cone-shaped structure, a stainless steel ball (206) is placed at the hollowed-out position, a through hole (204b-1) is formed in the hollowed-out position in a downward mode, and groove-shaped channels are formed in two sides of the upper portion of the hollowed-out position;

each one-way valve structure is characterized in that a cover body (204a) is provided with a shielding hole (204a-1) and two drain holes (204 a-2); the shielding hole (204a-1) is positioned at the top of the stainless steel ball (206), and the diameter of the shielding hole is smaller than that of the stainless steel ball (206); the discharge hole (204a-2) is communicated with the groove-shaped channel;

the cover body (204a) is fixedly connected with the base (204 b);

the push-pull pipe (201), the steel ball type one-way valve (204) and the filtering membrane part are sequentially arranged from top to bottom, and adjacent parts are fixedly connected;

the steel ball type one-way valve (204) is connected with the inner wall of the upper section part (101) in a sliding way;

the push-pull rod (301) passes through the center of the steel ball type check valve (204), and the two are connected in a sliding way.

8. A syringe as claimed in claim 1, wherein: the filtering membrane part comprises a filtering membrane (401) and a membrane bracket (402).

9. A syringe according to claim 8, wherein: the membrane bracket (402) comprises an upper layer and a lower layer, and the filter membrane (401) is clamped between the upper layer and the lower layer.

10. A syringe according to claim 8, wherein: the diameter of the filter hole of the filter membrane (401) is 0.22 mu m.

11. A syringe according to claim 8, wherein: the membrane bracket (402) is provided with more than two fan-shaped holes (403); the fan-shaped holes (403) are rotationally and symmetrically distributed around the central axis of the membrane bracket (402).

12. A syringe as claimed in claim 1, wherein: the injector is made of low-temperature resistant materials.

13. A syringe as claimed in claim 1, wherein: the injector is used for any combination of four operations; the four operations are as follows: injection of the cell preparation, washing of the cell preparation, cryopreservation of the cell preparation, and concentration of the cell preparation.

14. A syringe as claimed in claim 1, wherein: the upper end of the upper section part (101) is provided with a limiting handle (103).

15. A syringe as claimed in claim 1, wherein: the upper end of the push-pull pipe (201) is provided with a large piston handle (203).

16. A syringe as claimed in claim 1, wherein: the upper end of the push-pull rod (301) is provided with a small piston handle (303).

17. A syringe as claimed in claim 1, wherein: the head of the small piston (302) is conical or arc-shaped.